The candidate is pursuing a K23 career development award to conduct clinical research in the area of neuroimaging in multiple sclerosis (MS). This award will provide protected research time and training in preparation for independent R01 funding. The primary mentor for this project is Dr. Bruce Rosen, an expert in applying functional imaging tools to solve specific biological and clinical problems. Dr. Howard Weiner will serve as the secondary mentor, lending his renowned expertise in MS. Multiple sclerosis is the leading non- traumatic cause of disability in young adults. Cognitive dysfunction is common in MS and contributes to loss of employment and reduced quality of life. By exploring connectivity of brain regions, resting-state functional connectivity (fcMRI) has the potential to improve the understanding of MS pathogenesis while serving as a unique means of examining cognition. The candidate will correlate functional inter-hemispheric connectivity with measures of anatomical connectivity (diffusion tensor imaging in the corpus callosum) and corpus callosum atrophy, a common finding in MS. Correlating these measures will help evaluate the functional role of the corpus callosum in cognitive dysfunction in MS. We will also explore how cortical pathology, as demonstrated at ultra-high field (7T), affects connectivity in a locally constrained area, termed local connectivity. Both fcMRI at 3T and cortical lesion measures at 7T will be correlated with neuropsychological testing to help address how white and gray matter pathologies differentially contribute to cognitive dysfunction. In addition to mentored research activities, tailored didactic coursework and other training activities will provide formal educatio in imaging analysis and cognitive neuroscience to the candidate. ) PUBLIC HEALTH RELEVANCE: This study aims to provide insight into the cause of cognitive dysfunction in multiple sclerosis, a leading non-traumatic cause of disability in young adults, by examining resting state functional connectivity MRI. New functional markers of the disease will be developed for future application to monitor the effectiveness of new treatments for multiple sclerosis. This study may aid in the development of future therapies specifically targeted to prevent or improve cognitive dysfunction in multiple sclerosis.